All patients with suspected ovarian cancer (Raised CA 125 and a complex pelvic mass in a perimenopausal woman) were radiologically staged using CT scan and a chest x-ray. Patients with evidence of intra-abdominal metastasis and/or malignant pleural effusion were approached for entry to the study. Tissue biopsy was obtained either under radiological control (core needle biopsy) or via laparoscopic surgery (punch biopsy). Patients with histologicaly confirmed epithelial ovarian cancer were randomized to receive either three cycles of carboplatin (AUC 7) or paclitaxel (175 mg/m2).
The extracellular matrix protein TGFBI induces microtubule stabilization and sensitizes ovarian cancers to paclitaxel.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Metaplastic breast carcinomas display genomic and transcriptomic heterogeneity [corrected]. .
Disease
View SamplesExpression profiling of metaplastic carcinoma of the breast
Metaplastic breast carcinomas display genomic and transcriptomic heterogeneity [corrected]. .
Disease
View SamplesIn order to define the inhibitory activity of PMN-Ectosomes, we investigated the early gene expression profiles of resting and zymosan A-stimulated human monocyte-derived macrophages in the absence or presence of PMN-Ectosomes.
No associated publication
No sample metadata fields
View SamplesExpression of meningioma 1 (MN1) has been proposed to be a negative prognostic molecular marker in adult AML with normal cytogenetics, however its role in pediatric leukemia is unknown. We found elevated MN1 expression in 53 of 88 pediatric leukemia cases: significant amounts of MN1 were found in immature B-cell ALL and most cases of infant leukemia but no MN1 expression was detected in T-cell acute lymphoblastic leukemia (T-ALL). Interestingly 17 of 19 cases harboring MLL-X fusions showed also elevated MN1 expression. Lentiviral siRNA mediated MN1 knock-down resulted in cell cycle arrest and impaired clonogenic growth of 3 MLL-X-positive human leukemia cell lines overexpressing MN1 (THP-1, RS4;11, MOLM13). In a mouse MLL/ENL-induced leukemia MN1 overexpression resulted from retroviral provirus insertion. Strikingly co-expression of MN1 with MLL/ENL resulted in significantly reduced latency for induction of an AML phenotype in mice suggesting functional cooperation. MN1 overexpression in MLL/ENL-carrying cells resulted in expansion of the L-GMP population and facilitated disease induction in secondary recipients. Gene expression profiling allowed to define a number of potential MN1 hematopoietic targets. Up-regulation of CD34, FLT3, HLF, or DLK1 was validated in bone marrow transiently overexpressing MN1, in MN1-induced mouse leukemias, as well as in some cases of pediatric leukemias overexpressing MN1. Taken together, our work suggests that MN1 overexpression is essential for growth of leukemic cells, and that MN1 can act as a cooperating oncogene with MLL-X fusion genes most probably through modification of a distinct gene expression program that leads to expansion of a leukemia initiating cell population.
Functional characterization of high levels of meningioma 1 as collaborating oncogene in acute leukemia.
No sample metadata fields
View SamplesSkeletal muscle differentiation is a highly coordinated multistep process in which proliferating mononucleated myoblasts rst withdraw from the cell cycle, then differentiate into postmitotic mononucleated myocytes, and subsequently fuse into multinucleated myotubes which nally bundle to form mature muscle bers. All these processes are controlled by the sequential activation of myogenic regulatory factors, and especially MYOD1 is activated in the early phase to promote the transcription of muscle-specific genes coding for muscle proteins such as alpha-actin, myosin heavy chain and muscle creatine kinase.
No associated publication
Cell line
View SamplesSkeletal muscle differentiation is a highly coordinated multistep process in which proliferating mononucleated myoblasts rst withdraw from the cell cycle, then differentiate into postmitotic mononucleated myocytes, and subsequently fuse into multinucleated myotubes which nally bundle to form mature muscle bers. All these processes are controlled by the sequential activation of myogenic regulatory factors, and especially MYOD1 is activated in the early phase to promote the transcription of muscle-specific genes coding for muscle proteins such as alpha-actin, myosin heavy chain and muscle creatine kinase.
No associated publication
Cell line
View SamplesSince the first description of the involvement of Notch signaling in homeostasis especially of T cells, there is great effort in research to find new target genes of Notch that are involved in T cell development in the thymus. We developed a stroma cell free system that is able to induce T cell development in vitro called the plastic thymus. Having this new tool we decided to use the gene expression technique to get an expanded and more global picture of the changes in gene expression in T cell progenitor induced by Notch signaling via DLL4-Fc.
No associated publication
Cell line, Treatment
View SamplesHepatocellular carcinoma (HCC) is a heterogeneous disease, and despite considerable research efforts, no molecular classification of HCC has been introduced in clinical practice. The existing molecular classification systems were established using resected tumors, which introduces a selection bias towards patients without liver cirrhosis and with early stage HCCs. So far, these classification systems have not been validated in liver biopsy specimens from tumors diagnosed at intermediate and late stages. We generated and analyzed expression profiles from 60 HCC biopsies from an unselected patient population with all tumor stages. Unbiased clustering identified 3 HCC classes. Class membership correlated with survival, tumor size, and with Edmondson and BCLC stage. Most biopsy specimens could be assigned to the classes of published classification systems, demonstrating that gene expression profiles obtained from patients with early stage disease are preserved in all stages of HCC. When a reference set of healthy liver samples was integrated in the analysis, we observed that the differentially regulated genes up- or down-regulated in a given class relative to other classes were actually dysregulated in the same direction in all HCCs, with quantitative rather than qualitative differences between the molecular subclasses. With the exception of a subset of samples with a definitive -catenin gene signature, biological pathway analysis could not identify class specific pathways reflecting the activation of distinct oncogenic programs. Our results suggest that gene expression profiling of HCC biopsies has limited potential to direct therapies that target specific driver pathways, but can identify subgroups of patients with different prognosis.
Gene expression analysis of biopsy samples reveals critical limitations of transcriptome-based molecular classifications of hepatocellular carcinoma.
Specimen part, Disease, Disease stage
View SamplesPegylated interferon- (pegIFN-) has replaced un-modified recombinant IFN- for the treatment of chronic viral hepatitis because of its superior anti-viral efficacy that is generally attributed to improved pharmacokinetic properties. However, the pharmacodynamic effects of pegIFN- in the liver have not been studied. We analyzed pegIFN- induced signaling and gene regulation in paired liver biopsies obtained before treatment and during the first week after injection of pegIFN- in 18 patients. Despite sustained high serum concentrations of pegIFN- over the entire one-week dosing interval, IFN- signaling through the Jak-STAT pathway occurs only during the first day. PegIFN- induces hundreds of genes that can be classified into 4 clusters based on different temporal expression profiles. In all clusters, gene transcription is mainly driven by IFN stimulated gene factor 3 (ISGF3). IFN induced secondary transcription factors do not cause additional waves of gene expression. We could not confirm a role of un-phosphorylated STAT1 in prolonging IFN- induced gene transcription. Collectively, our results reveal that the major effects of pegIFN- in the liver are caused by an early and transient activation of ISGF3. Prolonging the serum half-life of IFN- does not necessarily improve its pharmacodynamic properties.
Pegylated IFN-α regulates hepatic gene expression through transient Jak/STAT activation.
Specimen part, Disease, Disease stage, Treatment, Subject, Time
View Samples